Modulation of gastric acid secretion by peripheral presynaptic alpha 2-adrenoceptors at both sympathetic and parasympathetic pathways

1. The effects of the alpha 2-adrenoceptor agonist detomidine, and the antagonists idazoxan and CH-38083 were examined on gastric acid secretion from non-vagotomized and vagotomized stomach lumen-perfused rats. The effects of detomidine on acid secretion from isolated guinea-pig gastric fundus were also evaluated. 2. In both non-vagotomized and vagotomized rats i.p. administration of detomidine significantly increased acid secretion, whereas i.c.v. detomidine was without effect. The stimulant action of i.p. detomidine was antagonized by both i.p. idazoxan and CH-38083 as well as by pretreatment with reserpine. 3. In vagotomized and reserpinized rats whose acid secretion was increased by electrical stimulation of the left vagus nerve, i.p. injection of detomidine caused inhibitory effects on acid secretion which were fully antagonized by both i.p. idazoxan and CH-38083. 4. Both idazoxan and CH-38083 caused a significant increase in acid secretion induced by vagal stimulation. At higher doses the two antagonists displayed a potentiating effect on vagally induced acid secretion only when they were associated to i.v. infusion of prazosin and propranolol. 5. Detomidine was without effect on acid secretion from isolated guinea-pig gastric fundus, whereas histamine or bethanechol caused a marked and dose-dependent stimulant action. 6. Overall, these results provide evidence that peripheral presynaptic alpha 2-adrenoceptors modulate both adrenergic inhibitory and cholinergic excitatory influences on rat gastric acid secretion.